HLAMatchmaker is a new algorithm to determine HLA compatibility at the structural level. Donor- recipient HLA matching is assessed by intralocus and interlocus comparisons of polymorphic amino acid tdplet sequences in alloantibody-accessible positions of HLA molecules. For many patients, HLAMatchmaker can identify mismatched HLA antigens that are zero-triplet mismatches and should therefore, be considered fully histocompatible at the structural level. Recent studies have shown that HLA class I triplet matching correlates with excellent kidney transplant outcome and that HLAMatchmaker provides a useful strategy to identify more compatible donors. After working with the various HLAMatchmaker programs downloaded from our website, many HLA professionals share our belief that this algorithm is superior to the conventional HLA matching system especially for sensitized patients as well as minority groups for whom it is often difficult to find compatible donors. This project deals with studies on refining and expanding the HLAMatchmaker algorithm and how this program can be used in a clinical setting. There are four objectives: (1) Study the serological identification of triplet-defined of epitopes recognized by human monoclonal alloantibodies, (2) Determine the relative immunogenicity of triplet-defined epitopes, (3) Assess clinical relevance of HLAMatchmaker in platelet transfusion support of refractory thrombocytopenic patients and stem cell transplantation from unrelated donors, (4) Apply HLAMatchmaker for determining the structural basis of HLA class II compatibility. These studies will increase our understanding of the structural basis of HLA compatibility. The ultimate goal of this project is the application of HLAMatchmaker as a new donor selection strategy in transplantation and platelet transfusions nationwide.